Corporate Presentation. January 2015

Transcription

1 Corporate Presentation January 2015

2 Forward Looking Statement This document does not constitute or form part of any offer or invitation to sell or issue, or any solicitation of any offer to purchase or subscribe for, any shares in the Company, nor shall any part of it nor the fact of its distribution form part of or be relied on in connection with any contract or investment decision relating thereto, nor does it constitute a recommendation regarding the securities of the Company. This document may contain forward-looking statements and estimates made by the Company, including with respect to the anticipated future performance of TiGenix and the market in which it operates. They include all matters that are not historical facts. Such statements, forecasts and estimates are based on various assumptions and assessments of known and unknown risks, uncertainties and other factors, which were deemed reasonable when made but may or may not prove to be correct. Actual events are difficult to predict and may depend upon factors that are beyond the Company's control. Therefore, actual results, the financial condition, performance or achievements of TiGenix, or industry results, may turn out to be materially different from any future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Forward-looking statements, forecasts and estimates only speak as of the date of this document and no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. TiGenix disclaims any obligation to update any such forwardlooking statement, forecast or estimates to reflect any change in the Company s expectations with regard thereto, or any change in events, conditions or circumstances on which any such statement, forecast or estimate is based. 2

3 Management Team with Proven Track Record of Success Managing Director and CEO: Eduardo Bravo, MBA More than 25 years experience in the pharma and biotech industries at Sanofi-Aventis, Recordati, Cephalon and SmithKline Beecham CFO: Claudia D Augusta, PhD More than 15 years experience in equity and debt financing at Aquanima (Santander Group), Apax Corporate Finance and Deloitte Corporate Finance CTO: Wilfried Dalemans, PhD More than 25 years experience in the pharma and biotech industries; previous engagements at GSK Biologicals and Transgène CMO: Marie Paule Richard, MD More than 25 years experience in the global biopharmaceutical industry at Aicuris, Crucell and Sanofi Pasteur VP Regulatory Affairs & Corporate Quality : María Pascual, PhD More than 10 years experience in cell therapy companies; specialized in regulatory affairs for advanced therapies; external adviser to EMA VP Medical Affairs & New Product Commercialization: Mary Carmen Diez, MD More than 20 years experience in the biopharmaceutical industry at Meda Pharma, Asta Médica, Pfizer and Dupont Pharma 3

4 Investment Highlights Pivotal Phase III Orphan Asset: Cx601 Perianal fistulas in Crohn s patients in the US & EU represents a multi-billion dollar market opportunity Pivotal Phase III allogeneic stem cell asset (local administration of a single dose) with data expected in 3Q2015 Phase II: 56% of patients achieved remission Clear US Approval Strategy: Cx601 Valuable Pipeline Opportunity: Cx611 Proprietary Technology Platform Established Uniform Manufacturing Commercialized Product: ChondroCelect Positive Type B meeting held with the FDA Agreement on key parameters of future US Phase III trial Use of data from pivotal Phase III trial in EU to support a BLA Application for SPA filed Q Intravenously-administered allogeneic stem cell product for rheumatoid arthritis (Phase II) and severe sepsis (Phase Ib already initiated) Positive phase IIa data in refractory RA Expanded adipose-derived stem cells (eascs) Acts by controlling inflammation Well defined and fully characterized products Consistent and robust manufacturing process Up to 360 billion cells can be obtained from one donor 2,400 doses of Cx601 and 4,000 doses of Cx611 First ever ATMP 1 approved by EMA; valuable experience in regulatory approval / commercialization process Indicated for the repair of cartilage defects in the knee Established national reimbursement and partnered with Swedish Orphan Biovitrium 1 Advanced Therapy Medicinal Product 4

5 Multiple Product Candidates in Clinical Development Product 1 Cell Type Indication Preclinical Phase I Phase II Phase III Market Cx601 (local) allogeneic adipose-derived stem cells complex perianal fistulas in Crohn s disease orphan drug (EU) Cx611 (intravenous) allogeneic adipose-derived stem cells rheumatoid arthritis severe sepsis Cx621 (intralymphatic) allogeneic adipose-derived stem cells autoimmune disorders ChondroCelect characterised autologous chondrocytes knee cartilage lesions partnered 2 1 Covered by 24 patent families 2 Distributed through Swedish Orphan Biovitrum ( Sobi ) and the Finnish Red Cross Blood Service

6 Clear US Strategy Defined for Cx601 Positive Type B meeting held with FDA in December 2013 Adequacy of the existing non-clinical package to support an IND 1 filing for a US-based pivotal Phase III trial Acceptability of using data from the ongoing ADMIRE-CD 2 Phase III study in Europe to support a biologic license application (BLA) Agreement on key parameters of future US pivotal Phase III trial Development plan for the US being implemented Selection of contract manufacturing organization for technology transfer (3Q 2014) Application for special protocol assessment (submission 4Q 2014) IND 1 to be filed as soon as technology transfer finalised Partnering discussions initiated 1 Investigational New Drug 2 Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn s Disease 6

7 MSCs 1 Interact Closely with the Immune System IFN-γ (ng/ml) TNF-α (ng/ml) ASCs PBMCs Activated PBMCs PBMCs+ASCs activated PBMCs+ASCs * * * p<0.05 relative to supernatant from activated PBMCs Source: De la Rosa et al. Tissue Engineering * The ability to interact with many players in the immune system qualify MSCs (including ASCs) as a potent anti-inflammatory agent % OF CD4+CD25+++ ON TOTAL CD ACTIVATED PBMCs ACTIVATED PBMCs + ASCs * p<0.05 relative to activated PBMCs without ASCs Source: Tigenix data 1 MSCs: Mesenchymal Stem Cells 7

8 eascs as a Preferred Source of MSCs Easily accessible Source and expansion Considerably higher yield than bone marrow Cell stability during expansion Low immunogenicity, no tissue matching needed Pharmacological profile Enables allogeneic use Demonstrated anti-inflammatory capabilities 8

9 Validated easc Platform Quality Consistent and robust manufacturing process Quality control parameters defined: Identity, Purity, Potency Safety No signs of toxicity, tumorigenicity, nor ectopic tissue growth in preclinical safety studies Clinical safety data obtained Efficacy Demonstrated control of inflammation in 5 different preclinical models, including different routes of administration Clinical efficacy demonstrated Reproducibility No tissue type matching needed, tissue dissociation and isolation of cells according to defined protocol, and expansion through a standardized cell culture process without pooling of cells 9

10 easc Manufacturing Schematic manufacturing overview Cellular expansion Isolation of Stromal Vascular Fraction (SVF) Freezing Cell Banks 10

11 Manufacturing Process Scheme Uniform manufacturing scheme for all products Liposuction Cell isolation and expansion Up to 360 billion cells can be obtained from 1 donor Finished product units at current doses (clinical trials): Master cell bank (cryo) 2,400 doses of Cx601 1 Frozen Drug Substance (FDS) 4,000 doses of Cx611 2 Finished Product 1 Based on ongoing Phase III trial (120M cells per patient) 2 Assumes 1 million eascs/ Kg, weight average 80Kgs 11

12 A Growing Patent Portfolio in Cell Therapy 24 patent families related to cell therapy products Pending & granted patents in over 20 jurisdictions including the US; expiry dates 2024 onwards Key patent for Cx601 (PCX007) granted in AU, RU, MX, IL and NZ Patent protects use of ASCs in treatment of fistula Complementary protection possible through additional patents under review Portfolio covers key features of TiGenix chondrocyte and stem cell platforms Expanded cell compositions and preparations Use of expanded cells in treatment of broad range of indications Cell preparation methods & delivery systems FTO for indications in clinical development confirmed by external counsels US: Morrison & Foerster Europe: Carpmaels & Ransford 12

13 Cx601 Local injection of eascs for the treatment of complex perianal fistulas in Crohn s disease patients 13

14 Perianal Fistulas A Common Severe Complication of Crohn s Disease Fistulas: sores or ulcers that tunnel through the affected area into surrounding tissues 12% of Crohn s patients are affected by perianal fistulas 1 80% of these are complex Affect anal sphincters Present multiple tracts Are recurrent Are often associated with perianal abscess Fistula > 100,000 Crohn s patients suffer from complex perianal fistulas every year in Europe and the US alone => compromised QoL, pain, depression, risk of anal epithelial carcinoma 1 Source: >60 publications (including Schwartz 2002, Lapidus 2006), the European Federation of Crohn s and Colitis Associations, US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics 14

15 Perianal Fistulas: Treatment Options and Shortfalls Treatment Options Efficacy Safety Antibiotics No long term healing data 1 Safety concerns with prolonged use Immunossuppressants Low healing rates Relapse on drug cessation 2 High risk of infectious complications Infliximab (Remicade) Remission 23% 3 20% need dose increase 2 High rate of relapse 4 Safety remains a concern with long term use of biologics Adalimumab (Humira) Remission 33% 5 20% need dose increase 2 High rate of relapse 4 Safety remains a concern with long term use of biologics Surgery High proportion of recurrence 6 High risk of anal incontinence % recurrence within 4 months of cessation of treatment (Bnernstein LH et al. (1980). Gastroenterology 79: ) 2 Pearson DC et al. (1995) Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis. Ann Intern Med 123: ACCENT II clinical trial 4 54% for infliximab after 1 year (Sands BE et al. (2004). N Engl J Med 350: CHARM clinical trial 6 Schouten at al, Mizrahi et al, Sonoda et al, van der Hagen et al 7 A. Soltani, A. Kaiser, Diseases of the Colon & Rectum vol.53:4 (2010) 15

16 Market Potential: Perianal Fistula in Crohn s Disease Estimated peak year sales Assumptions: Population EU28 + US: 824 million Prevalence of Crohn s disease: 0.105% (865,200 patients) 1 Launch EU: 2017 Launch US: 2020 $ Milllion % CD patients with fistula 2 (approximately 121,100 patients) 12% 14% 16% % Complex fistula all fistula 3 (approximately 97,000 patients) 60% 80% 100% % Patients failing biologic 4 (approximately 77,500 patients) 70% 80% 90% % Market share (approximately 27,100 patients) 20% 35% 50% Average selling price $34k Note: Patient numbers refer to mid-point of the range given $21k $48k 1 TiGenix epidemiology report based on multiple publications 2 Schwartz et al, 2002, Vavricka et al., 2010, Pittet et al., 2010, KOL Interviews 3 Pittet et al., 2010, KOL Interviews 4 Sands et al., 2004, Lichtiger et al., 2010, KOL Interviews 16

17 Cx601: Developing a New Treatment Paradigm >10 years of experience, consistent efficacy and safety Cx401 (autologous) Phase I Phase II Phase III (FATT 1) 3 5 I patients 1 center Crohn s and non-crohn s perianal fistulas: 75% efficacy; open 1 50 patients 3 centers Crohn s and non-crohn s perianal fistulas: 71% efficacy; p<0, patients 19 centers Non-Crohn s perianal fistulas: 41% efficacy; p (n.s.) 4 Cx601 (allogeneic) Phase II 34 patients 6 centers Crohn s perianal fistulas: 56% efficacy; open 5 Phase II, IIS 6 (ALOREVA) 7 10 patients 1 center Rectovaginal fistulas: 60% efficacy; open Phase III (ADMIRE-CD) 8 Note: Patient data refers to number of patients recruited 289 patients 52 centers 1 García Olmo, et al., Diseases of the Colon & Rectum 2 García Olmo, et al., Diseases of the Colon & Rectum 3 Fistula Advanced Therapy Trial 4 Herreros, et al., Diseases of the Colon & Rectum 5 de la Portilla, F. et al., Int. Journal of Colorectal Disease 6 Investigator Initiated Study 7 Allogeneic adipose stem cells in rectovaginal fistulas 8 Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn s Disease 17

18 Cx601: Phase II Proof of concept for an allogeneic therapy TRIAL SUMMARY Start June 2009 Completion September 2010 Conditions Study design Enrollment Complex perianal fistula in Crohn s patients Single arm Non-controlled Safety/Efficacy study One fistula/tract treated Maximum of 2 doses 1 34 patients recruited; 24 treated # of centers 6 sites Primary endpoint Secondary endpoints Incidence of treatment emergent adverse-events Closure of external openings (clinically and MRI) Reduce number of draining fistulas Efficacy 56% PATIENT SELECTION Older than 18 years: both genders Complex perianal fistula fulfilling some of the following conditions: Associated fecal incontinence Risk factors of anal incontinence At least 1 previous treatment for a fistulous disorder Crohn s disease (CDAI 200) Less than 3 fistulous tracts Wash out of anti-tnf of at least 8 weeks prior to inclusion No concomitant administration of anti- TNF allowed during the duration of the trial Efficacy confirmed by second gastroenterologist not involved in the direct care of the patient 1 First dose of 20M cells; Second dose of 40M cells injected if fistula has not closed after 12 weeks 18

19 Cx601: Phase II Results Safety of allogeneic cells confirmed Repeated treatment with allogeneic eascs well tolerated Favorable side effect profile Overview of adverse events. Full analysis set (n=24) Patients with at least one TEAE 1 during the study: 13 (54.2%) Patients with at least one TEAE possibly related to eascs during the study 5 (20.8%) Serious adverse events reported leading to withdrawal 2 2 (8.3%) (Events considered to be possibly related to the study treatment; no clinically relevant abnormalities found during physical examination or in vital signs) 1 Treatment Emergent Adverse Event 2 Local abscess and pyrexia 19

20 Cx601: Phase II Results Allogeneic eascs confirmed efficacy of autologous cells Reduction in number of draining fistulas Closure of external openings of treated fistula tracts 70% 60% 50% 40% 50,0% Nº fistulas: 61,5% % 60% 50% 40% 38,1% 56,3% 30% 30% 20% 10% 10,0% 7,7% 20% 10% 0% -10% 12 weeks (N=20) 24 weeks (N=13) 0% -10% 12 weeks (N=21) 24 weeks (N=16) N= Patients with available information. Missing data not included in percentage calculations Reduction of drainage in fistulas that have not achieved complete closure Significant efficacy in complete closure of treated fistula tracts No spontaneous healing of non-treated fistula tracts Note: Patients who received only one dose were evaluated at weeks 12 and 24; Patients who received 2 doses were evaluated at weeks 12 and 26 20

21 Cx601: Investigator-Initiated Study ALOREVA Therapeutic effect of eascs also confirmed in extremely tough condition TRIAL SUMMARY Start September 2009 Completion December 2011 Conditions Study design Enrollment Rectovaginal fistulas (RV) in Crohn s patients Open label Non-controlled Safety and efficacy study 10 patients # of centers 1 site Primary endpoint Secondary endpoints Efficacy Safety and feasibility of Cx601 for the treatment of RV fistula in Crohn s patients Clinically relevant variations in laboratory test Preliminary efficacy data 60% (1 year) PATIENT SELECTION and RESULTS PATIENT Women SELECTION of a childbearing and RESULTS age (>18) Rectovaginal fistula Patients with Crohn s disease diagnosed at least 12 months earlier with either one previous surgery for fistulous disease or a physical status which discourage liposuction Anti-TNF treatment not allowed during the duration of the trial. Wash out period of 8 weeks prior to inclusion 5 patients completed the study. The other 5 were rescued with anti-tnf due to Crohn s flares 3 out of these showed complete closure of the fistula 9 out the 10 patients had their fistula closed at some point during the study 21

22 Cx601: Phase III ADMIRE-CD Trial Robust Phase III designed to qualify as a single pivotal study TRIAL SUMMARY Start July 2012 Completion Condition Study design Enrollment Ongoing Complex perianal fistula in Crohn s patients Randomized, double blind, placebo controlled trial All tracts treated. Fixed single dose patients recruited # of centers 52 sites in 8 countries Primary endpoint Secondary endpoints Remission 2 at week 24 Response 3 Time to remission / time to response PDAI score and QoL assessment (IBDQ 4 ) PATIENT SELECTION Older than 18 years: both genders Patients with perianal fistulizing Crohn s disease refractory to antibiotics, immunosuppressants and/or anti-tnf Exclusion of naïve patients Limit of patients refractory to antibiotics to < 25% of total recruited patients 2 internal openings (fistulas) and 3 external openings (tracts) Non active luminal CD (CDAI 5 220) CD diagnosed for 6 months; Fistula draining < 6 weeks prior to inclusion Concomitant treatments allowed without modification of treatment dose or regimen million cells 2 Closure of all draining tracts at baseline despite gentle finger compression confirmed by MRI (no collections > 2cm) 3 Closure of 50% draining tracts at baseline despite gentle finger compression confirmed by MRI (no collections > 2cm) 4 Inflammatory Bowel Disease Questionnaire 5 Crohn's Disease Activity Index 22

23 Cx601: Phase III ADMIRE-CD Trial Robust Phase III designed to qualify as a single pivotal study Statistical plan: Evaluations at weeks 6, 12, 18 and 24 (after dosing) Final evaluation at week 52 Blind clinical and MRI assessment Statistical pre-determination: α = β = 0.20 Power: Designed for finding at least 25% difference among study groups Patient enrollment: completed Follow-up: Initial follow up of six months completed with 1 year long-term follow-up study expected 3Q 2015 and 1Q 2016, respectively 23

24 Cx611 Intravenous injection of eascs for the treatment of early rheumatoid arthritis 24

25 Rheumatoid Arthritis: A Huge Market Opportunity On a dollar basis, the market is dominated by biologic drugs (>80% of the market), and especially by antibodies which block tumor necrosis factor TNF 1 (5 out of the 9 currently approved biologicals 2 ) TNFα inhibitors dominate the market with yearly average cost of ~$19k The overall RA market is expected to grow at a CAGR of slightly above 7% to approximately $23.4Bn in 2016 Despite a wide variety of therapeutic options, a high level of unmet patient need exists Early Rheumatoid Arthritis Induce and maintain low disease activity Target acute & inflammatory disease state Indication of activity evidenced in refractory patients in Phase IIa trial 1 Wiki Analysis: Arthritis Drug market 2 Humira, Enbrel, Remicade, Simponi and Cimzia 25

26 eascs are Functional in RA Models Arthritic score after three i.v. doses of eascs TNF - alpha IL - 10 % cytokine-secreting T cells % cytokine-secreting T cells * p<0.001 * p<0.001 Days after treatment Source: TiGenix data on file Source: González-Rey et al. Ann. Rheum. Dis Intravenous administration of eascs does protect animals from rapid progress to arthritic joints (CIA model) T cells from RA patients reduce their inflammatory profile upon contact with eascs (in vitro experiment) 26

27 Phase IIa Trial First randomised trial with eascs in refractory RA patients TRIAL SUMMARY Start March 2011 Completion January 2013 Condition Study design Enrollment Patients with RA refractory to at least two biologics Dose escalation, single blind, placebo-controlled (Cx611+ DMARD 1 vs. placebo + DMARD) 53 patients # of centers 23 sites Primary endpoint Secondary endpoints Safety (tolerability and treatmentemergent adverse events) Efficacy measured by: ACR 2 remission (ACR 20, ACR50, ACR 70) EULAR 3 (DAS 4 28, VSG 5 ) Imaging (RAMRIS) Quality of life (SF-36) PATIENT SELECTION Heterogeneous patient population: Median range of diagnoses 5 69 years Patients with severe grade of RA: Median DAS 28 score: Patients refractory to at least two biologics Mean nº of previous DMARDs: 3.38 => 74% of patients received 3 or more DMARDs Mean nº of previous biologics: 2.92 => 45% of patients received 3 or more biologics 66% of patients had received Enbrel 64% of patients had received Humira 51% of patients had received Infliximab 1 DMARD: Disease-modifying anti-rheumatic drugs 2 American College of Rheumatology 3 European League Against Rheumatism 4 Disease Activity Score 5 Variable Surface Glycoprotein 27

28 Phase IIa Trial Favorable safety profile of all three doses of Cx611 Safety profile Cx611+DMARD (N=46) Placebo+DMARD (N=7) Patients with any adverse events (AE) 38 (83%) 4 (57%) Patients with any related AE 22 (48%) 1 (14%) Patients with any grade 3-4 related AE 1 (2%) 1 (14%) Patients with any AE leading to discontinuation 1 (2%) 0 (0%) Only one patient experienced a serious adverse event leading to discontinuation of the treatment 1 All other side effects were mild and transient: most common related adverse events in the Cx611+DMARD group: fever (15%), headache (9%), asthenia (6%) 1 Lacunar infarction, which is defined as a type of stroke in the brain's deep structures 28

29 Phase IIa Results Encouraging therapeutic activity EULAR criteria EULAR response DAS 28 (CRP) <3.2 Good + Moderate % % % M1 M2 M3 FV M6 (FV) M1 M2 M3 FV M6 (FV) DAS 28 (CRP) <2.6 (remission) M1 M2 M3 FV M6 (FV) Cx611 + DMARD Placebo + DMARD Results shown are response rates in percentage M1, M2, M3 and M6 (FV) refers to month 1, 2, 3 and 6 (Final Visit) respectively; For all graphs: N=46 for Cx611+DMARD cohort and N=7 for placebo + DMARD cohort 29

30 Cx611 Intravenous injection of eascs for the treatment of severe sepsis 30

31 eascs Can Protect in Severe Sepsis LPS Model CLP Model Source: Gonzalez-Rey, 2009 * p<0.001 Cx611 reduces mortality in animal models of sepsis This effect is due to a combination of reducing pro-inflammatory and increasing antiinflammatory mediators, production of anti-microbial effectors and increased phagocytosis 31

32 Phase I trial synopsis and rational Evaluation of the therapeutic effect of ASCs on the inflammatory response to LPS in healthy volunteers TRIAL SUMMARY Start Q Expected completion Objective Study design Enrolment # of centres Primary endpoint Q Effect of ASCs on inflammatory response to LPS Placebo-controlled dose-ranging study (3 doses) Randomization scheme: 3:1 32 healthy volunteers 1 (Academic Medical Center, University of Amsterdam) Vital signs and symptoms Laboratory measures and functional assays of innate immunity PATIENT SELECTION and RESULTS Rational Model mimics clinical signs of sepsis Fever, chills Headache, myalgia Nausea Mild tachycardia Insignificant change in blood pressure Genomic response similar as in sepsis (not the case for animal studies) Provides proof-of-principle - essential information on the mechanism of action of ASCs to counteract the consequences of an LPS exposure Results will guide for a proposed phase II study in severe sepsis 32

33 ChondroCelect Characterized autologous chondrocytes for the treatment of cartilage lesions in the knee 33

34 ChondroCelect First ever ATMP approved by EMA (2009) First, and so far, only cell therapy product with national reimbursement Suspension of characterized autologous chondrocytes injected intra-articularly Indicated for the repair of single symptomatic cartilage defects of the femoral condyle of the knee (ICRS III or IV) in adults Market: Between 17,000 28,000 new patients per year in Europe Additional expansion opportunity ex-europe and Middle East Currently on the market in BE, NL, ES, UK and Finland => 2013 gross sales of 4.3M Further market penetration to be achieved through distribution agreement with Swedish Orphan International (Sobi), effective as of 1st June % royalty on ChondroCelect net sales (22% in year 1) and reimbursement of almost all ChondroCelect expenses => ChondroCelect becomes a cash-flow positive asset for TiGenix 1 Sobi Territory: European Union (excl. Finland), Switzerland, Norway, Russia, Turkey and the MENA region, whereby certain countries within MENA will only become part of Sobi s territory as of Nov. 12 th,

35 Key Milestones, Facts and Investment Highlights 35

36 Key Milestones Product Cx601 (local) Europe US 4Q14 Phase 3 enrollment completed ü ü 3Q15 primary endpoint results (24 weeks) 3Q14 CMO selection ü 4Q14 SPA submission 1Q16 study results (1 year follow-up) 1H16 EMA filing 1H17 EU launch 1H16 tech transfer finalized 2H16 pivotal Phase 3 initiated Cx611 (IV) RA Severe Sepsis ü 4Q15 Phase 2 enrollment initiated 4Q14 Phase 1b initiated YE16 Phase 2 enrollment completed 2Q15 Phase 1b study results 4Q15 Phase 2 enrollment initiated 1H17 Phase 2 study results YE17 Phase 2 study results 2Q17 Phase 2 enrollment completed ChondroCelect Increase market penetration in existing countries Expand geographic reach through new market entry 36

37 Key Facts about TiGenix Headquarter Operations Employees Stock Exchange Leuven, Belgium Madrid, Spain Approximately 50 employees Traded on NYSE Euronext Brussels (TIG) Market Capitalization Approximately $105M Reference Shareholders Liquidity Analyst Coverage 26% held by Grifols and Novartis 74% free-float of which 30% held by institutional investors 6 analysts covering the stock, of which four are independent Funds available $22,5M as of 30 th of September Exchange rate as of 30 September 2014 (oanda) 37

38 Investment Highlights Pivotal Phase III Orphan Asset: Cx601 Perianal fistulas in Crohn s patients in the US & EU represents a multi-billion dollar market opportunity Pivotal Phase III allogeneic stem cell asset (local administration of a single dose) with data expected in 3Q2015 Phase II: 56% of patients achieved remission Clear US Approval Strategy: Cx601 Valuable Pipeline Opportunity: Cx611 Proprietary Technology Platform Established Uniform Manufacturing Commercialized Product: ChondroCelect Positive Type B meeting held with the FDA Agreement on key parameters of future US Phase III trial Use of data from pivotal Phase III trial in EU to support a BLA Application for SPA filed Q Intravenously-administered allogeneic stem cell product for rheumatoid arthritis (Phase II) and severe sepsis (Phase Ib already initiated) Positive phase IIa data in refractory RA Expanded adipose-derived stem cells (eascs) Acts by controlling inflammation Well defined and fully characterized products Consistent and robust manufacturing process Up to 360 billion cells can be obtained from one donor 2,400 doses of Cx601 and 4,000 doses of Cx611 First ever ATMP 1 approved by EMA; valuable experience in regulatory approval / commercialization process Indicated for the repair of cartilage defects in the knee Established national reimbursement and partnered with Swedish Orphan Biovitrium 1 Advanced Therapy Medicinal Product 38

39 Corporate Presentation November